Alzheimer's disease (AD) is the major cause of dementia with more
than 35 million patients suffering from this disease, which has no
cure. In this project a long-term partnership will be established
between academia and companies to better understand the role of prion
protein in AD and to develop new molecular entities for diagnostic and
therapeutic applications.

This project combines a consortium from social, medical, and
technological sciences with industry, academia and end user
organisations, with the primary objective of developing an information
and communications technology (ICT) based platform to identify and
manage community dwelling older adults at risk of functional decline
and frailty. Within this project, our major activities adhere to the
tenants of our commitment at the European Innovation Partnership of
Active and Healthy Ageing Action Group 3 related to nutrition, in
particular to the development of an interative website for nutrition.

3. "Detoxification of toxic oligormers using natural products", 2012-2013,
coordinated by The University of Sheffield, with FCUL as the participating institution, PI FCUL: A. P. Rauter

4. "Towards the development of molecular probes for investigating drug targets in amyloid diseases", 2011-2012,
coordinated by The University of Sheffield, with FCUL as the participating institution, PI FCUL: A. P. Rauter

III. National StrategicFramework's Program (QREN) and Foundation for Science and Technology (FCT) funded projects

This project deals with the design, synthesis and biological
evaluation of new potential antitumor agents intended to inhibit
cyclin-dependent kinases, which are ATP-dependent enzymes that regulate
cell cycle progression and whose abnormal activity or overexpression
play a crucial role in the development of cancer.

6. "New drugs from sugars against infection caused by pathogenic
Bacillus species (FACIB)", funded by QREN within the Incentive System
to Research & Technological Development to companies â��projects in
co-promotion (QREN SI I&DT Co-Promotion program),
Lisboa-01-0202-FEDER-021547, 2011-2014,
extended to February 2015, coordinated by CIPAN-Industrial Company for
the Production of Antibiotics, in co-promotion with FCUL, PI FCUL: A.
P: Rauter

In this project a new family of antibacterial glycosides is
explored, that have shown a selective activity against Bacillus
species, in particular against Bacillus anthracis, the cause of
anthrax, a primarily disease of hoofed herbivores and a bioterrorism
agent. In this project, bridging of chemistry and biology leads to
novel molecular entities with new mechanisms of action, currently under
investigation.

The project aims to determine the chemical and nutritional profiles,
as well as the antioxidant, antitumoral and neuroprotective properties
of halophytes from the Algarve. Valorization of halophytes in terms of
the biological properties already found in the halophytes studied, will
be based on their potential application as food additives.

The main goal of this project dealt with the valorization of the
plant Genista tenera, an antidiabetic medicinal plant from Madeira
Island, by identifying its active principles for
nutraceutical/medicinal purposes. Investigation of various plant
extracts regarding their antidiabetic, antioxidant and
anticholinesterase activities, toxicity and phytochemical studies led
to the selection of the most potent extract, in which the plant active
principle was identified as 8-Î²-D-glucosylgenistein. Its synthesis,
biological studies and absence of toxicity, together with the results
obtained regarding its interaction with amyloid peptides identified
this compound as a promising lead for diabetes and the frequently
associated Alzheimer's disease.

The natural products Miharamycins are potent inhibitors of the
fungus Pyricularia oryzae, that destroys rice cultures and is
considered a bioterrorism agent. These molecules are structurally quite
complex, embodying a nucleoside with a 2-aminopurine N9-Î²-linked to a
bicyclic saccharide moiety, elongated to an amino acid of unknown
stereochemistry, N-linked to L-arginine (Miharamycin B) or its hydroxy
derivative (miharamycin A). The greatest challenge of this project was
based on the assignment of the unknown stereochemistry of these
molecules and the first synthesis of its core structure. These goals
were fully achieved and a small library of compounds was also generated
aiming to access new compounds structurally more simple than the
natural products for structure/activity relationship studies. The
anticholinesterase activity of the new intermediate nucleosides was
evaluated and the N9-Î²-linked structures were not active, as desired
for their investigation as pesticide leads. Interestingly, the
N7-Î²-linked nucleosides exhibited, some of them, a selective and
potent butyrylcholinesterase (BChE) inhibition, opening a new line of
research based on these structures for the production of new molecular
entities to study the progression of Alzheimer's disease in late
stages, where acetylcholinesterase levels have decreased and BChE
levels increased considerably. The project was carried out in
collaboration with the Université Pierre et Marie Curie within a joint
Ph.D. program (Filipa Marcelo).

10. "Study of Salvia species crop production aiming at the
evaluation of their constituents for the potential control of
Alzheimer's disease", funded by FCT, PTDC/AGR-AAM/66414/2006, 2007-2010,
coordinated by Escola Superior AgrÃ¡ria do Instituto Politécnico de
Santarém with FFCUL as participant Institution, PI of FFCUL: A. P.
Rauter

Salvia sclareoides is an Iberian endemism which extracts
demonstrated unique properties as acetylcholinesterase inhibitors, more
potent than rivastigmine, a drug marketed for the treatment of AD in
the early disease stages. The phytochemical study of the plant
identified the triterpene and phenolic components. Amongst the latter
group of compounds, the major product, rosmarinic acid, has
anticholinesterase activity and recently, in 2013, we could demonstrate
by NMR a new binding site for this compound, opening the way to a new
line of research based on these findings. This research was developed
in collaboration with Dr. Filipa Marcelo (Universidade Nova de Lisboa)
and Prof. Jesus Jimenez Barbero (Centro de Investigaciones Biologicas,
Consejo Superior de Investigaciones Científicas, in Spain).This plant
also showed a significant antiproliferative effect on human
neuroblastome cells (collaboration with Prof. Margarida Meireles,
CQB-FCUL) and stabilized the normal and soluble Prion protein by
preventing its conformational changes, that cause the formation of
plaques and vacuoles in the brain occurring in transmissible spongiform
encephalopathies (TSEs), also known as prion diseases, in humans and
animals, for which no therapy is available. The latter study was
conducted in collaboration with The Sheffield University in UK, within
PCBNet approved projects with the Carbohydrate Chemistry Group.The
biological properties of the plant and identified components, and the
absence of toxicity of its extracts, encouraged further research, up to
the present time, including the Ph.D. research program on this plant of
Dr. Isabel Branco (Ph. D., UL).

Our contribution to this project was based on the generation of a
small library of biologically active sugar derivatives by synthesis,
and elucidation of their structure for structure/activity relationship
studies. The most promising results were patented in Europe and in USA.

12. "Synthesis, chemistry and photophysics of nanoencapsulated
anthocyanins. Development of a new concept of food dyes with
anthocyanins", funded by FCT, POCTI/QUI/38884/2001, 2001-2004,
coordinated by Instituto Superior Técnico of Universidade Técnica de
Lisboa, with Fundação da Faculdade de Ciências da Universidade de
Lisboa as participant Institution, PI of FFCUL: A. P. Rauter

Within this project, we have synthesized a small library of new
anthocyanins, highly reactive and unstable, which structure could be
characterized by NMR.